P6 Reverses the Protective Effect of IL-6 Cytokines on NMDA-induced Toxicity.

<p><b>A</b>–<b>B</b>, Primary cortical neurons (A) or SH-SY5Y cells (B) were pretreated with P6 (0.5 µM) for 1 h, and then grown in the presence of P6 and IL-6 plus sIL-6R or OSM for 1 h, and then in the presence of cytokine, P6, plus NMDA for an additional 24 h. Cell viability was determined by the MTT reduction assay. Graphic representation of the mean ± SEM of triplicate cultures in three separate experiments. ***p<0.001 compared to control; **p<0.001, *p<0.01, and ♦p<0.05 compared to NMDA; and ?p<0.001 and #p<0.01 compared to NMDA plus cytokines. <b>C</b>–<b>D</b>, P6 Inhibits IL-6 Cytokine-induced STAT3 Activation. Primary neurons (C) or SH-SY5Y cells (D) were grown with P6 for 1 h and where indicated, grown in the presence of OSM or IL-6 plus sIL-6R and P6. The levels of phosphorylated STAT3 Tyr705, phosphorylated STAT3 Ser727, and total STAT3 were analyzed at the indicated time points. The densitometric ratios of P-STAT3 Tyr705 or P-STAT3 Ser727 versus total STAT3 were calculated, and shown as Fold Increase. Graph represents the mean ± SEM of triplicate cultures in four separate experiments. *<i>p</i><0.001 and **p<0.01 compared to control; and ?p<0.001, #p<0.01, and &p<0.05 compared to IL-6 plus IL-6R or OSM alone.